An example of an autosomal recessive trait is spider lamb syndrome, or hereditary chondrodysplasia. Lambs affected with this syndrome display several skeletal abnormalities, including disproportionately long “spider” legs, curvature of the spine, facial deformities, rib and sternum deformities, lack of body fat, and muscular atrophy. The causative mutation is a single base-pair substitution, from a T to an A, altering a highly conserved amino acid in the fibroblast growth factor receptor 3 (FGFR-3) gene. This prevents the receptor from functioning to limit endochondral ossification and thus bone growth.¹

Dominant Inheritance

Traits or diseases with a dominant mode of inheritance only require one affected allele to express the trait or disease, also known as the affected phenotype, and there is no distinguishable difference in the affected phenotype of a heterozygote and homozygote. Again, the genes that are responsible for these traits or diseases can be on the autosomes or sex chromosomes. Dominant traits or diseases may be caused by gain-of-function mutations that enable the mutant protein to have an altered structure or function. Alternatively, a single, functional copy of a gene may not be enough to achieve normal levels of function (“haploinsufficient”), resulting in the need for two normal copies of the gene to achieve a normal phenotype.

The main feature of an autosomal dominant trait or disorder is that affected individuals must have at least one affected parent (unless it is a new mutation), and thus the disorder does not skip generations. There is no sex bias with an autosomal dominant trait, and approximately half the offspring of a heterozygous affected individual bred to a normal individual will be affected. Breeding two heterozygous affected individuals will result in 75% affected (one third of which are homozygous and two thirds of which are heterozygous) and 25% normal offspring.

An example of an autosomal dominant disease is myotonia in goats. When startled or making sudden, forceful movements, these goats can develop severe, acute muscle stiffness causing immobility and sometimes falling over, resulting in descriptions such as “fainting,” “nervous,” “stiff-legged,” or “epileptic” goats. A single nucleotide change, from a G to a C, was identified that substituted a proline amino acid for a conserved alanine in a chloride channel in the muscle fibers. This alteration in the chloride channel causes a diminished channel-open probability at voltages near the resting membrane potential of skeletal muscle, resulting in decreased chloride conductance and a significantly decreased electrical threshold for firing action potentials. Ultimately, this altered chloride channel allows conduction of repetitive impulses that result in sustained muscle fiber contraction and stiffness.²

Co-dominant Inheritance

The co-dominant (or semi-dominant) pattern of inheritance is distinguished by the fact that homozygotes can be differentiated from heterozygotes based on clinical features. A well-known example of a co-dominant disease is hyperkalemic periodic paralysis (HYPP) in Quarter Horses. In HYPP the voltage-gated sodium channels in the muscle fibers have a mutation that increases sodium permeability across the skeletal muscle cell membrane. This causes increased muscle mass, but also drooling, prolapse of the nictitating membrane (“third eyelid”), respiratory stridor, and weakness. Homozygous HYPP horses experience more frequent and severe clinical signs of disease than heterozygous horses.³ Thus, it is important to counsel breeders to avoid producing homozygous affected horses by not mating two heterozygous horses, since approximately 25% of their offspring would be expected to be homozygous affected and 50% would be heterozygous, while only 25% would be homozygous normal. Breeding a heterozygous horse to an unaffected horse will also result in approximately 50% of the offspring being heterozygous with no possibility of producing a homozygous affected foal.